The Heart of the Alzheimer's: A Mindful View of Heart Disease

Evangelisti, Alessandro; Butler, Helen; Monte, Federica del

doi:10.3389/fphys.2020.625974

Cited by 10 publications

(4 citation statements)

References 178 publications

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“…Based on this hypothesis, the cardiac pulsation in AD patients may be altered 10 and fAPF is able to reveal it. Recent findings showed that heart failure may co-occur in AD patients with the prevalence of one third of cases 11 .…”

Section: Resultsmentioning

confidence: 99%

Fractional amplitude of physiological fluctuations of resting state fNIRS in Alzheimer’s disease patient and healthy control

Ferdinando

Moradi

Korhonen

et al. 2023

Neural Imaging and Sensing 2023

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Functional magnetic resonance imaging (fMRI) is a common medical device to diagnose Alzheimer's disease (AD), but it is not for all subjects due to its cost and other issues. We investigated the potential of functional near-infrared spectroscopy (fNIRS) to separate AD patients from controls as a pre-screening prior to more thorough examination using fMRI. For this purpose, two-channel fNIRS device with 690 nm and 830 nm, sampled at 10 Hz, was placed on the forehead with 3 cm distance between light source and detector to provide resting state fNIRS signals from both sides of pre-frontal cortex. We applied fractional amplitude of physiological fluctuation (fAPF), modified from fractional amplitude of low frequency fluctuation (fALFF), to oxy-, deoxy-, and total-hemoglobin in very low frequency (0.008-0.1 Hz), respiratory (0.1-0.6 Hz), and cardiac (0.6-5 Hz) bands. A t-test at 0.05 significance level was used to evaluate if the fAPF score from AD patients and healthy controls is significantly different. We found that fAPF score of total hemoglobin from both side at cardiac band showed its potential to distinguish AD patients from healthy controls. This finding was in-line with the recent finding that heart failure may co-occur in AD patients with the prevalence of one third of cases.

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Section: Resultsmentioning

confidence: 99%

Fractional amplitude of physiological fluctuations of resting state fNIRS in Alzheimer’s disease patient and healthy control

Ferdinando

Moradi

Korhonen

et al. 2023

Neural Imaging and Sensing 2023

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show abstract

“…7b ). Accumulation of protein aggregates marked by hyperphosphorylation of Tau is a well-known hallmark of Alzheimer’s disease, but it has also been linked to the pathogenesis of heart disease 37 . Using an antibody recognizing phospho-Tau S385 in mice, corresponding to S396 in human, we observed lower levels of phosphorylated Tau in hearts lacking ErbB2 and/or ERRα, suggesting that this proteotoxic stress is not an underlying cause of the observed DCM in these mice (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Integrated multi-omics analysis of adverse cardiac remodeling and metabolic inflexibility upon ErbB2 and ERRα deficiency

et al. 2022

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Functional oncogenic links between ErbB2 and ERRα in HER2+ breast cancer patients support a therapeutic benefit of co-targeted therapies. However, ErbB2 and ERRα also play key roles in heart physiology, and this approach could pose a potential liability to cardiovascular health. Herein, using integrated phosphoproteomic, transcriptomic and metabolic profiling, we uncovered molecular mechanisms associated with the adverse remodeling of cardiac functions in mice with combined attenuation of ErbB2 and ERRα activity. Genetic disruption of both effectors results in profound effects on cardiomyocyte architecture, inflammatory response and metabolism, the latter leading to a decrease in fatty acyl-carnitine species further increasing the reliance on glucose as a metabolic fuel, a hallmark of failing hearts. Furthermore, integrated omics signatures of ERRα loss-of-function and doxorubicin treatment exhibit common features of chemotherapeutic cardiotoxicity. These findings thus reveal potential cardiovascular risks in discrete combination therapies in the treatment of breast and other cancers.

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“…2 In the heart, proteotoxicity is now recognized to promote ventricular dysfunction and cardiomyopathy. 3,4 In addition, amyloidosis predictably develops in the human atrium with aging, exceeding 90% in the ninth decade of life, and its presence is linked to AF. 5 In this senile form of amyloid, natriuretic peptides have been implicated: atrial deposits are uniformly immunoreactive for ANP (atrial natriuretic peptide), while BNP (B-type natriuretic peptide) has also been detected.…”

mentioning

confidence: 99%

Natriuretic Peptide Oligomers Cause Proarrhythmic Metabolic and Electrophysiological Effects in Atrial Myocytes

Yang

Subati

Kim

et al. 2022

Circ: Arrhythmia and Electrophysiology

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Background: With aging, the human atrium invariably develops amyloid composed of ANP (atrial natriuretic peptide) and BNP (B-type natriuretic peptide). Preamyloid oligomers are the primary cytotoxic species in amyloidosis, and they accumulate in the atrium during human hypertension and a murine hypertensive model of atrial fibrillation susceptibility. We tested the hypothesis that preamyloid oligomers derived from natriuretic peptides cause cytotoxic and electrophysiological effects in atrial cells that promote arrhythmia susceptibility and that oligomer formation is enhanced for a mutant form of ANP linked to familial atrial fibrillation. Methods: Oligomerization was assessed by Western blot analysis. Bioenergic profiling was performed using the Seahorse platform. Mitochondrial dynamics were investigated with immunostaining and gene expression quantitated using RT quantitative polymerase chain reaction. Action potentials and ionic currents were recorded using patch-clamp methods and intracellular calcium measured using Fura-2. Results: Oligomer formation was markedly accelerated for mutant ANP (mutANP) compared with WT (wild type) ANP. Oligomers derived from ANP, BNP, and mutANP suppressed mitochondrial function in atrial HL-1 cardiomyocytes, associated with increased superoxide generation and reduced biogenesis, while monomers had no effects. In hypertensive mice, atrial cardiomyocytes displayed reduced action potential duration and maximal dV/dT of phase 0, with an elevated resting membrane potential, compared with normotensive mice. Similar changes were observed when atrial cells were exposed to oligomers. mutANP monomers produced similar electrophysiological effects as mutANP oligomers, likely due to accelerated oligomer formation, while ANP and BNP monomers did not. Oligomers decreased Na + current, inward rectifier K + current, and L-type Ca ++ current, while increasing sustained and transient outward K + currents, to account for these effects. Conclusions: These findings provide compelling evidence that natriuretic peptide oligomers are novel mediators of atrial arrhythmia susceptibility. Moreover, the accelerated oligomerization by mutANP supports a role for these mediators in the pathophysiology of this mutation in atrial fibrillation.

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The Heart of the Alzheimer's: A Mindful View of Heart Disease

Cited by 10 publications

References 178 publications

Fractional amplitude of physiological fluctuations of resting state fNIRS in Alzheimer’s disease patient and healthy control

Fractional amplitude of physiological fluctuations of resting state fNIRS in Alzheimer’s disease patient and healthy control

Integrated multi-omics analysis of adverse cardiac remodeling and metabolic inflexibility upon ErbB2 and ERRα deficiency

Natriuretic Peptide Oligomers Cause Proarrhythmic Metabolic and Electrophysiological Effects in Atrial Myocytes

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